Tan Choo Hock, Liew Jia Lee, Navanesan Suerialoasan, Sim Kae Shin, Tan Nget Hong, Tan Kae Yi
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
J Venom Anim Toxins Incl Trop Dis. 2020 Jul 17;26:e20200013. doi: 10.1590/1678-9199-JVATITD-2020-0013. eCollection 2020.
The Asiatic pit vipers from the complex are medically important venomous snakes. These pit vipers are often associated with snakebite that leads to fatal coagulopathy and tissue necrosis. The cytotoxic venoms of spp.; however, hold great potential for the development of peptide-based anticancer drugs.
This study investigated the cytotoxic effect of the venom from , the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue.
The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study.
Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian venom and suggested its anticancer potential in drug discovery.
该属的亚洲蝮蛇是具有重要医学意义的毒蛇。这些蝮蛇常与导致致命性凝血病和组织坏死的蛇咬伤相关。然而,某些种的细胞毒性毒液在基于肽的抗癌药物开发方面具有巨大潜力。
本研究调查了原产于马来西亚的红树林蝮蛇(也称为海岸蝮蛇)的毒液对一组来自乳腺、肺、结肠和前列腺的人类癌细胞系以及各组织相应正常细胞系的细胞毒性作用。
该毒液对所有测试细胞系均表现出剂量依赖性细胞毒性活性,中位抑制浓度(IC)范围为0.42至6.98μg/mL。该毒液对乳腺癌细胞系(MCF7)具有高选择性指数(SI = 14.54),表明其对癌细胞的细胞毒性明显高于正常细胞系。此外,使用C18反相高效液相色谱对毒液进行分级分离,并检测各蛋白组分的抗癌效果。发现含有一种亲水性低分子量(约7.5 kDa)蛋白质的组分1对乳腺癌细胞系(MCF7)具有最强的细胞毒性和选择性。使用液相色谱 - 串联质谱法将该蛋白质鉴定为本研究中称为紫斑蝮蛇素的一种毒液解整合素。
综上所述,这些发现揭示了从马来西亚红树林蝮蛇毒液中分离出的一种解整合素蛋白具有强大且选择性的细胞毒性,并表明了其在药物发现中的抗癌潜力。